Protein kinase profiling in miscarriage: implications for the pathogenesis of trisomic pregnancy.

Trisomy in pregnancy increases risks of miscarriage, fetal anomalies, and perinatal complications, with trisomy 16 the most common trisomy in human conceptions. The pathogenesis and protein expression profiles in trisomic pregnancy have not been well elucidated. Our objective was to profile protein kinase expression in trisomic and chromosomally normal miscarriage.
Placental chorionic villus cultures were set up from first-trimester miscarriages (n = 73). Protein kinases (n = 75) were profiled using a 2D Western blot in cultures from trisomic miscarriages (n = 6) (trisomy 16 or trisomy 15) and compared to chromosomally normal (euploid) miscarriages (n = 4).
Distinct patterns of protein kinase expression were seen in the two trisomic groups, including dosage-dependent over-expression of the chromosome 16-encoded ERK1 in trisomy 16. This supports a role for chromosome-specific effects in the pathogenesis of trisomy (gene dosage hypothesis). In addition, both trisomic groups had increased inter-individual variation in protein kinase expression, which supports a role for amplified sensitivity to environmental and genetic variation in the pathogenesis of trisomy (amplified instability hypothesis).
Both gene dosage effects and amplified instability operate simultaneously on the expression of protein kinases in trisomic pregnancies ending in miscarriage.
AuthorsPaul J Yong, Deborah E McFadden, Wendy P Robinson
JournalJournal of obstetrics and gynaecology Canada : JOGC = Journal d'obstétrique et gynécologie du Canada : JOGC (J Obstet Gynaecol Can) Vol. 34 Issue 12 Pg. 1141-8 (Dec 2012) ISSN: 1701-2163 [Print] Canada
PMID23231796 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Protein Kinases
  • Abortion, Spontaneous (genetics, pathology)
  • Chorionic Villi (pathology, physiology)
  • Chromosomes, Human, Pair 15 (genetics)
  • Chromosomes, Human, Pair 16 (genetics)
  • Female
  • Gene Amplification
  • Gene Dosage
  • Gene Expression Profiling
  • Genetic Variation
  • Genome-Wide Association Study
  • Humans
  • Mosaicism
  • Pregnancy
  • Protein Kinases (genetics)
  • Trisomy (genetics)

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